The IgE-mediated secretory response of sensitized basophils or mast cells to appropriate antigen is the initiating event of reactions of immediate hypersensitivity. In addition to the characteristic release of histamine, it is now recognized that a variety of additional chemical mediators are also released by this process. The net result of this event is the induction of a localized inflammatory response; it is the unrestrained development of this localized inflammation that is responsible for the pathogenesis of extrinsic bronchial asthma and other allergic diseases. With the onset of the inflammatory phase, basophils and mast cells become exposed to a variety of inflammatory reactants. Prominent reactants of inflammatory reaction include antibody or complement-coated surfaces or particles. It has been demonstrated recently that serum-treated zymosan particles, although causing no release alone, markedly augmented IgE-mediated histamine release from human basophils. The results suggested that C3b receptors on basophils mediated the enhancement. It is postulated that a similar interaction in vivo may constitute an important mechanism of the amplification of immediate hypersensitivity reactions and contribute to the pathogenesis of allergic disease. The goals of this proposal are therefore four-fold. First, direct evidence will be sought for the participation of basophil C3b and Fc receptors in the augmented release. Secondly, the probability that phagocytic stimuli likewise augment IgE-mediated histamine release from human lung mast cells will be evaluated. Thirdly, studies will be directed to elucidating the mechanism of enhancement. Fourthly, the possibility that the IgE-mediated release of additional basophil and mast cell mediators is similarly enhanced will be determined.